Dental stem cells for regeneration of calvarial bone defects in rats
The aim of this project is to identify new strategies for regeneration of complex bone defects using novel and minimally-invasive sources of sources of stem cells and their secretory products. Bone defects resulting from trauma, ablative surgery and pathology are a serious clinical problem. The current clinical standard for treatment of such defects is the use of autogenous bone grafts which require additional surgical procedures and involve additional morbidity for patients – often requiring hospitalization and sick-leave. Thus, there is a clear clinical need for developing new techniques for bone regeneration to avoid invasive grafting procedures.
Stem cell therapy is one such alternative. Transplanting bone marrow stem cells in combination with various biomaterials into bone defects has shown promising results in preclinical and clinical studies. However, bone marrow is also invasive to harvest and may not always yield high quality stem cells, especially in older patients. Dental tissues such as gingiva are much less invasive to harvest and are routinely removed during dental surgery. Thus, dental tissue may provide a less-invasive alternative to bone marrow as a source of stem cells for bone regeneration. Moreover, the growth factors released from these cells may themselves promote bone regeneration to a similar degree as the cells themselves. Using cellular growth factors instead of cells may further simplify and mitigate costs of treatment in future applications. Developing novel cost-effective strategies for regeneration of complex bone defects would have a clear clinical relevance and benefit to both patients and healthcare providers.
Preliminary in vitro experiments have been performed to confirm the presence of stem cells in these dental tissues, and the bone regeneration potential of the cells and their secretions. However, the true potential of these strategies must be confirmed in well-designed and adequately powered animal studies before they may be recommended for clinical application. Therefore, the specific objective of this animal study is to test the in vivo bone regeneration potential of stem cells from human dental tissues or bone marrow and their secretions in skull-bone defects of rats.
The calvarial (skull) bone defect model is one of the most frequently reported models for bone regeneration in the literature and is well established in our group. The surgical procedure is performed under general anesthesia with pre- and post-operative analgesic administrations to the animals (severity grade: mild-to-moderate). We aim to test different cells and their secretions in combination with different biomaterials to identify the most effective and clinically relevant strategy for bone regeneration. From calculations based on previous experiments, we estimate that a total of 160 rats will be used in this study.
Certain measures will be taken to reduce the number of animals required, such as preparation of two skull defects (one on each side of the midline) per animal, thus allowing us to test two experimental groups per animal and maximize the output per animal (3Rs). All recommended protocols to minimize pain and distress will be followed such as regular monitoring and the use of specific Welfare Assessment Scoresheets. Individual animals will be monitored for signs of distress, pain or suffering to ensure that severity does not exceed the estimated level (moderate). At appropriate study endpoints the animals will be euthanized following recommendations from the local animal facility.
Stem cell therapy is one such alternative. Transplanting bone marrow stem cells in combination with various biomaterials into bone defects has shown promising results in preclinical and clinical studies. However, bone marrow is also invasive to harvest and may not always yield high quality stem cells, especially in older patients. Dental tissues such as gingiva are much less invasive to harvest and are routinely removed during dental surgery. Thus, dental tissue may provide a less-invasive alternative to bone marrow as a source of stem cells for bone regeneration. Moreover, the growth factors released from these cells may themselves promote bone regeneration to a similar degree as the cells themselves. Using cellular growth factors instead of cells may further simplify and mitigate costs of treatment in future applications. Developing novel cost-effective strategies for regeneration of complex bone defects would have a clear clinical relevance and benefit to both patients and healthcare providers.
Preliminary in vitro experiments have been performed to confirm the presence of stem cells in these dental tissues, and the bone regeneration potential of the cells and their secretions. However, the true potential of these strategies must be confirmed in well-designed and adequately powered animal studies before they may be recommended for clinical application. Therefore, the specific objective of this animal study is to test the in vivo bone regeneration potential of stem cells from human dental tissues or bone marrow and their secretions in skull-bone defects of rats.
The calvarial (skull) bone defect model is one of the most frequently reported models for bone regeneration in the literature and is well established in our group. The surgical procedure is performed under general anesthesia with pre- and post-operative analgesic administrations to the animals (severity grade: mild-to-moderate). We aim to test different cells and their secretions in combination with different biomaterials to identify the most effective and clinically relevant strategy for bone regeneration. From calculations based on previous experiments, we estimate that a total of 160 rats will be used in this study.
Certain measures will be taken to reduce the number of animals required, such as preparation of two skull defects (one on each side of the midline) per animal, thus allowing us to test two experimental groups per animal and maximize the output per animal (3Rs). All recommended protocols to minimize pain and distress will be followed such as regular monitoring and the use of specific Welfare Assessment Scoresheets. Individual animals will be monitored for signs of distress, pain or suffering to ensure that severity does not exceed the estimated level (moderate). At appropriate study endpoints the animals will be euthanized following recommendations from the local animal facility.